Simian Immunodeficiency Virus (SIV)<i>gag</i>DNA-Vaccinated Rhesus Monkeys Develop Secondary Cytotoxic T-Lymphocyte Responses and Control Viral Replication after Pathogenic SIV Infection

Egan, Michael A.; Charini, William A.; Kuroda, Marcelo J.; Schmitz, Jörn E.; Rácz, Paul; Tenner-Rácz, Klara; Manson, Kelledy; Wyand, Michael S.; Lifton, Michelle A.; Nickerson, Christie E.; Fu, Tong-Ming; Shiver, John W.; Letvin, Norman L.

doi:10.1128/jvi.74.16.7485-7495.2000

Cited by 136 publications

(93 citation statements)

References 48 publications

(30 reference statements)

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“…The efficacy parameters in Table 3.1 relate only to adults in the partially protected class (zero efficacy is assumed for the unprotected class). 3.2.5 For vaccines A, B and C, which are disease-modifying, the VE I and VE P parameters are consistent with what one would expect for an HIV vaccine that reduces the logarithm of the HIV viral load by two units, a reduction that would appear to be achievable on the basis of candidate vaccines tested in non-human primates (Shiver et al, 2002;Barouch et al, 2000;Egan et al, 2000). These VE I and VE P parameters are derived from estimates of the increase in HIV infectiousness per unit increase in the logarithm of the HIV viral load, q I , and the increase in the rate of progression to AIDS per unit increase in the logarithm of the HIV viral load, q P .…”

Section: 2supporting

confidence: 54%

The potential effect of an HIV/AIDS vaccine in South Africa

Johnson¹,

Dorrington²

2007

S. A. Act. J.

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This paper presents a model for assessing the potential effect of an HIV/AIDS vaccine in South Africa, and for calculating the amount of vaccine that would be required. A number of different hypothetical vaccine profiles and vaccine distribution strategies are considered. Results suggest that a sterilising vaccine could reduce the HIV incidence between 2015 and 2025 by up to 50%, while a disease modifying vaccine would be unlikely to reduce HIV incidence by more than a third. The effect on AIDS mortality over the same period would be substantially smaller, and it is unlikely that any preventive vaccine would reduce AIDS mortality by more than 10% between 2015 and 2025.

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Section: 2supporting

confidence: 54%

The potential effect of an HIV/AIDS vaccine in South Africa

Johnson¹,

Dorrington²

2007

S. A. Act. J.

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“…The SIVsmE660-challenged monkeys received only a plasmid gag DNA vaccine, while the SHIV-89.6P-infected monkeys received cytokineaugmented plasmid gag and env DNA vaccines. Therefore, the potency of the vaccine-elicited CTL responses was lower in the monkeys eventually challenged with SIVsmE660 than in those challenged with SHIV-89.6P (2,4,10). In the setting of less potent CTL responses, higher levels of viral replication and an associated generation of larger numbers of new mutant viruses would be expected.…”

Section: Discussionmentioning

confidence: 99%

Simian-Human Immunodeficiency Virus Escape from Cytotoxic T-Lymphocyte Recognition at a Structurally Constrained Epitope

Peyerl

Barouch

Yeh

et al. 2003

J Virol

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Virus-specific cytotoxic T lymphocytes (CTL) exert intense selection pressure on replicating simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) in infected individuals. The immunodominant Mamu-A * 01-restricted Gag p11C, C-M epitope is highly conserved among all sequenced isolates of SIV and therefore likely is structurally constrained. The strategies used by virus isolates to mutate away from an immunodominant epitope-specific CTL response are not well defined. Here we demonstrate that the emergence of a position 2 p11C, C-M epitope substitution (T47I) in a simian-human immunodeficiency virus (SHIV) strain 89.6P-infected Mamu-A * 01 ؉ monkey is temporally correlated with the emergence of a flanking isoleucine-to-valine substitution at position 71 (I71V) of the capsid protein. An analysis of the SIV and HIV-2 sequences from the Los Alamos HIV Sequence Database revealed a significant association between any position 2 p11C, C-M epitope mutation and the I71V mutation. The T47I mutation alone is associated with significant decreases in viral protein expression, infectivity, and replication, and these deficiencies are restored to wild-type levels with the introduction of the flanking I71V mutation. Together, these data suggest that a compensatory mutation is selected for in SHIV strain 89.6P to facilitate the escape of that virus from CTL recognition of the dominant p11C, C-M epitope.

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“…Although HIV vaccine strategies designed to elicit a high frequency of CD8 ϩ T lymphocytes are being pursued, little attention has been paid to the breadth of these immune responses. Because vaccine-induced CD8 ϩ T lymphocytes mediate control of viremia and therefore slow clinical progression in SIV-or simian human immunodeficiency virus (SHIV)-infected rhesus monkeys (13)(14)(15)(16), investigators are developing vaccine modalities that increase the magnitude of virus-specific CD8 ϩ T lymphocyte responses (17). However, an effective vaccine-elicited CD8 ϩ T lymphocyte response must recognize a diversity of epitopes so as to minimize the impact of individual viral epitope escape mutations.…”

Section: Irus-specific Cd8mentioning

confidence: 99%

Immunodomination in the Evolution of Dominant Epitope-Specific CD8+ T Lymphocyte Responses in Simian Immunodeficiency Virus-Infected Rhesus Monkeys

Newberg

McEvers

Gorgone

et al. 2006

The Journal of Immunology

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Because the control of HIV-1 replication is largely dependent on CD8+ T lymphocyte responses specific for immunodominant viral epitopes, vaccine strategies that increase the breadth of dominant epitope-specific responses should contribute to containing HIV-1 spread. Developing strategies to elicit such broad immune responses will require an understanding of the mechanisms responsible for focusing CD8+ T lymphocyte recognition on a limited number of epitopes. To explore this biology, we identified cohorts of rhesus monkeys that expressed the MHC class I molecules Mamu-A*01, Mamu-A*02, or both, and assessed the evolution of their dominant epitope-specific CD8+ T lymphocyte responses (Gag p11C- and Tat TL8-specific in the Mamu-A*01+ and Nef p199RY-specific in the Mamu-A*02+ monkeys) following acute SIV infection. The Mamu-A*02+ monkeys that also expressed Mamu-A*01 exhibited a significant delay in the evolution of the CD8+ T lymphocyte responses specific for the dominant Mamu-A*02-restricted SIV epitope, Nef p199RY. This delay in kinetics was not due to differences in viral load kinetics or magnitude or in viral escape mutations, but was associated with the evolution of the Mamu-A*01-restricted CD8+ T lymphocyte responses to the highly dominant SIV epitopes Gag p11C and Tat TL8. Thus, the evolution of dominant epitope-specific CD8+ T lymphocyte responses can be suppressed by other dominant epitope-specific responses, and this immunodomination is important in determining the kinetics of dominant epitope-specific responses.

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Simian Immunodeficiency Virus (SIV)gagDNA-Vaccinated Rhesus Monkeys Develop Secondary Cytotoxic T-Lymphocyte Responses and Control Viral Replication after Pathogenic SIV Infection

Cited by 136 publications

References 48 publications

The potential effect of an HIV/AIDS vaccine in South Africa

The potential effect of an HIV/AIDS vaccine in South Africa

Simian-Human Immunodeficiency Virus Escape from Cytotoxic T-Lymphocyte Recognition at a Structurally Constrained Epitope

Immunodomination in the Evolution of Dominant Epitope-Specific CD8+ T Lymphocyte Responses in Simian Immunodeficiency Virus-Infected Rhesus Monkeys

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